The present invention relates to the murine monoclonal antibodies C, F and H specific to a major neutralizing epitope of influenza H5 hemagglutinin of clade 2.3 and active fragments thereof. The present invention also relates to methods and compositions for the prophylaxis and treatment of H5N1 influenza using murine monoclonal antibodies C, F or H or active fragments thereof. The present invention additionally relates to methods and compositions for providing universal protection against H5 influenza viruses using murine monoclonal antibodies C, F or H or fragments thereof together with a complementary murine monoclonal antibody or active fragments thereof. The present invention further relates to methods and compositions for the characterization and quantification of H5 expression using these murine monoclonal antibody or fragments thereof.
The publications and other materials used herein to illuminate the background of the invention or provide additional details respecting the practice, are incorporated by reference, and for convenience are respectively grouped in the Bibliography.
The recent emergence of H5N1 strains of influenza A virus and the high mortality caused by them in humans has raised concerns for the possibility of a future influenza pandemic. Preventive and therapeutic measures against circulating H5N1 strains have received a lot of interest and effort globally to prevent another pandemic outbreak. Present vaccine strategies have been hindered by antigenic variation of the influenza strains. Present vaccine strategies requiring endogenous synthesis of antibodies will not provide immediate protection against H5N1 infections in the event of a pandemic. Currently licensed antiviral drugs include the M2 ion-channel inhibitors (rimantidine and amantidine) and the neuraminidase inhibitors (oseltamivir and zanamivir). The H5N1 viruses are known to be resistant to the M2 ion-channel inhibitors (Biegel et al., 2005). Newer strains of H5N1 viruses are being isolated which are also resistant to the neuraminidase inhibitors, i.e, oseltamivir and zanamivir (Le et al., 2008; de Jong et al., 2005). The neuraminidase inhibitors also require high doses and prolonged treatment (de Jong and Hien, 2006), increasing the likelihood of unwanted side effects. Hence, alternative strategies for treatment of influenza are warranted.
Passive immunotherapy using monoclonal antibodies has been viewed as a viable option for treatment of many infectious diseases. Currently, there has been a lot of focus on therapeutic approaches using neutralizing antibodies against the HA1 protein of the influenza virus. This protein is easy to target as it is on the surface of the virus and antibodies against this protein can neutralize the virus efficiently. Hence, monoclonal antibodies (Mabs) against neutralizing epitopes of H5 hemagglutinin (HA) may be an attractive alternative to active vaccination of humans, in particular for those individuals who are at high risk from influenza infection, viz. the immuno-compromised patients or the elderly who do not respond well to active immunization. It is important that any Mab product should offer broad protection against circulating strains of H5N1 influenza and should prevent the selection of neutralization escape mutants in vivo. One technique to increase protection against circulating strains of H5N1 influenza and to prevent escape mutants is a combination therapy using complementary Mabs (Prabakaran et al., 2009).
It is desired to identify monoclonal antibodies that target major neutralizing epitopes of influenza H5 hemagglutinin of clade 2.3. It is also desired to identify monoclonal antibodies that can be used for the prophylaxis and treatment of H5N1 influenza. It is further desired to identify monoclonal antibodies that can be used to provide universal protection against H5 influenza viruses. It is also desired to identify monoclonal antibodies that can be used for the identification, characterization and/or quantification of H5 expression.